The genetic and cytogenetic bases of inherited diseases, especially those associated with mental retardation, will be assessed through an integrated application of tissue culture, somatic cell hybridization, cytogenetic studies and related techniques. Emphasis will be placed upon gene mapping, analysis of mammalian regulatory genes, methods of introducing foreign genetic material into cultured cells, and the study of DNA repair defects. The results obtained will be used to elucidate the etiology and pathogenesis of various inherited diseases, especially those associated with mental retardation, and to develop new therapeutic approaches.